Body composition, fat distribution and insulin sensitivity before and after weight reduction will be determined in post-menopausal (50-60 yr), obese women (n=36) who are homozygous for the W64R (Beta 3 AR mutation (MM, n=12), heterozygous (NM, n=12), or homozygous for the wild gene (NN, n=12). Using the post-obese (metabolically stable) state will uncover differences in insulin sensitivity otherwise confounded by the presence of obesity. These studies will help define the role of the W64R (Beta 3 AR mutation in the regulation of insulin sensitivity in post-menopausal women. We have screened 380 volunteers during the past year of which 33 have been included in the project and have been studied for the basal characterization and are currently in the weight loss program. Three of them had finished the whole program and had been re-tested. A new wave of recruitment initiated at the end of the year and is actually ongoing. Preliminary results have been presented in intramural meetings three times and in two extramural meetings. A report of the preliminary data has actually been generated to be sent to the Diabetes Journal next month. Taking into account the progress attained, we can say that about 35% of the project has been completed to this date. This timetable makes it very likely that the project will be completed on time for the period of support.